The provision of antiretroviral therapy (ART) in sub-Saharan Africa has influenced the clinical and public health environments in profound ways. While the individual-level effects of ART are well known, the impact of ART on HIV epidemic dynamics remains poorly understood. Although reduced infectivity of people on ART should lower HIV incidence, this could be counterbalanced by the longer duration of exposure due to the increased survival of people on ART. Our overall aim is to develop a scientifically rigorous mathematical model linked to unique field-based data from KwaZulu/Natal, South Africa, to determine optimal HIV treatment and prevention strategies in diverse social environments. We propose to use mathematical models, a rich and unique South African dataset and primary data collection to study the impact of ART on HIV epidemic dynamics including HIV prevalence and incidence, life expectancy, mortality and incidence of AIDS. The STDSIM model, initially developed to better understand the contrasting results of the Mwanza and Rakai sexually transmitted disease intervention trials, will be extended to include important aspects of HIV transmission, antiretroviral therapy, social environments and cost-effectiveness analysis. Our main partner site, the Africa Centre for Health and Population Studies (AC) in KwaZulu/Natal, South Africa has conducted population-based demographic surveillance on over 90,000 people in 11,000 households since 2000;since 2003 HIV sero-prevalence data have been collected. Detailed demographic, economic, geographic, behavioral and biological data are collected and updated twice a year. In addition, the AC, in partnership with the South African Department of Health runs an ART treatment program with over 2500 people on treatment and 5000 people in care, awaiting treatment. This rich and unique dataset is available for analysis and will feed into the development of the mathematical model. In addition, economic data will be collected on the costs of HIV treatment and voluntary counseling and testing services to perform cost-effectiveness analyses. PUBLIC HEALTH RELEVANCE To better understand the impact of antiretroviral therapy (ART) on HIV epidemic dynamics, we will develop a mathematical model using primary data collection and secondary analysis of a unique set of biological, behavioral, economic, geographical and clinical characteristics of a population in KwaZulu/Natal, South Africa.